The proposal addresses four major questions. First it proposes to confirm that VIP is an effective pharmacologic and physiologic modulator of acute lung injury. These studies will include time course evaluations of administering exogenous VIP before and after the insult; and to determine the distribution of endogenous VIP expression in lung following paraquat; xanthine-xanthine oxidase and NMDA (n-methyl d-aspartate) "neurogenic lung injury". The second aim will characterize the location and quantify VIP gene expression in normal lungs and neural tissues and determine the relationship between injuries, VIP gene expression and peptide synthesis and release. The Third aim proposes to define the pathogentic role of NO in acute oxidant lung injury by determining NO gene expression and the effects of NO "sinks" on oxidant injury; and to determine if the NO is of iNOS or cNOS origin. The last aim proposes to evaluate the mechanisms of lung protection by VIP and related peptides by determining the sequence of events leading to lung injury, the roles of NO and poly-ADP ribosylation; interactions between NO and VIP and relative potency of VIP related peptides in inhibiting the injuries to determine structural requirements for the effect.